Valinemia

Synonyms of Valinemia

Hypervalinemia

Valine Transaminase Deficiency

General Discussion

Valinemia is a very rare metabolic disorder. It is characterized by elevated levels of the amino acid valine in the blood and urine caused by a deficiency of the enzyme valine transaminase. This enzyme is needed in the breakdown (metabolism) of valine. Infants with valinemia usually have a lack of appetite, vomit frequently, and fail to thrive. Low muscle tone (hypotonia) and hyperactivity also occur.

The breakdown of valine involves at least seven stages and a deficiency of the appropriate enzyme at any of these stages leads to a disorder of varying severity and rarity.

Signs & Symptoms

Valinemia is usually present at birth. Symptoms in the newborn period include protein intolerance, metabolic acidosis, frequent vomiting, failure to thrive, and coma. The condition may become life-threatening. The levels of the amino acid valine in the blood and urine are elevated. Abnormally low muscle tone, excessive drowsiness, and/or hyperactivity can also occur.

Causes

Valinemia is a recessive genetic disorder. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

Valinemia is a rare disorder, occurring once in about 250,000 live births in the United States. It is present in affected infants at birth.

Related Disorders

Maple syrup urine disease (MSUD) is an extremely rare inherited metabolic disorder characterized by a distinctive sweet odor of the urine and sweat. It is a serious disorder that, unless treated promptly and correctly, can be life threatening. Therapy must be started at the earliest possible age to achieve the best results. MSUD is manageable, just as diabetes is manageable, but care and attention must be given to diet and to the treatment of even minor illnesses.

Symptoms develop because the body is unable to break down (metabolize) three of the essential amino acids, leucine, isoleucine, and valine. They are essential because they are used by the body to build proteins, and they are three of 11 amino acids that must be obtained as part of the daily diet since the body cannot synthesize them. These three amino aids share a common characteristic of chemical structure and are thus known as the branched chain amino acids (BCAAs). An affected newborn will present with abnormally high concentrations of acidic metabolic by-products of the BCAAs in the blood and other tissues (metabolic acidosis) that, if left untreated, may lead to seizures or coma, and may be life-threatening.

Propionic acidemia is a rare metabolic disorder characterized by deficiency of propionyl CoA carboxylase, an enzyme involved in the breakdown (catabolism) of the chemical “building blocks” (amino acids) of certain proteins. Symptoms most commonly become apparent during the first weeks of life and may include abnormally diminished muscle tone (hypotonia), poor feeding, vomiting, listlessness (lethargy), excessive loss of fluids from bodily tissues (dehydration), and episodes of uncontrolled electrical activity in the brain (seizures). Without appropriate treatment, coma and potentially life-threatening complications may result. In rare cases, the condition may become apparent later during infancy and may be associated with less severe symptoms and findings. Propionic acidemia is inherited as an autosomal recessive trait.

The methylmalonic acidemias are organic acidemias caused by an enzymatic defect in the metabolism of four amino acids (methionine, threonine, isoleucine and valine). This results in an abnormally high level of acid in the blood (academia) and body tissues. In the acute form, drowsiness, coma, and seizures may occur. Mental retardation is a long-term consequence. The disorder may be caused by a deficiency of one or more of the enzymes methylmalonyl CoA mutase, methylmalonyl racemase, or adenosylcobalamin synthetic enzymes. Excretion of methylmalonate, a product of amino acid metabolism, in the urine is abnormally high and therefore is a marker of the disorder. All known organic acidemias are inherited as autosomal recessive traits.

Multiple carboxylase deficiency is a genetic metabolic disorder that leads to impaired activity of three enzymes that are dependent on the vitamin biotin: propionyl CoA carboxylase, beta-methylcrotonyl CoA carboxylase, and pyruvate carboxylase. This condition results from a defect in cellular biotin transport or metabolism. Symptoms of the disorder include acidity of the blood and body tissues (acidosis), a widespread red skin rash, baldness, and slowed physical development. The disorder occurs in both a neonatal and a late-onset form and is treatable.

Diagnosis

Diagnosis depends on the precise laboratory identification and measurement of metabolic products that accumulate in the blood and urine. Sophisticated chromatographic equipment is required to identify these metabolites.

Standard Therapies

Treatment

A diet low in valine introduced during early infancy usually improves symptoms of valinemia, and lowers the valine concentrations in the blood to normal levels.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

Years Published

1988, 1989, 2003, 2007

The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.

The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.

NORD's Rare Disease Database provides brief introductions for patients and their families to more than 1,200 rare diseases. This is not a comprehensive database since there are nearly 7,000 diseases considered rare in the U.S. We add new topics as we are able to do so, with the help of rare disease medical experts.

If you are seeking information about a rare disease that is not in this database, we would suggest contacting the Genetic and Rare Diseases Information Center (GARD) at the National Institutes of Health. NIH has the most complete database of rare diseases in the U.S.

Representatives of patient organizations whose medical advisors are interested in assisting NORD in creating a report on a disease not currently covered in this database may write to orphan@rarediseases.org.